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Enhanced processivity of Dnmt1 by monoubiquitinated histone H3
Author(s) -
Mishima Yuichi,
Brueckner Laura,
Takahashi Saori,
Kawakami Toru,
Otani Junji,
Shinohara Akira,
Takeshita Kohei,
Garvilles Ronald Garingalao,
Watanabe Mikio,
Sakai Norio,
Takeshima Hideyuki,
Nachtegael Charlotte,
Nishiyama Atsuya,
Nakanishi Makoto,
Arita Kyohei,
Nakashima Kinichi,
Hojo Hironobu,
Suetake Isao
Publication year - 2020
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12732
Subject(s) - biology , dnmt1 , dna methyltransferase , histone h3 , dna methylation , histone , epigenomics , histone methyltransferase , methyltransferase , microbiology and biotechnology , dna , methylation , biochemistry , gene , gene expression
DNA methylation controls gene expression, and once established, DNA methylation patterns are faithfully copied during DNA replication by the maintenance DNA methyltransferase Dnmt1. In vivo , Dnmt1 interacts with Uhrf1, which recognizes hemimethylated CpGs. Recently, we reported that Uhrf1‐catalyzed K18‐ and K23‐ubiquitinated histone H3 binds to the N‐terminal region (the replication focus targeting sequence, RFTS) of Dnmt1 to stimulate its methyltransferase activity. However, it is not yet fully understood how ubiquitinated histone H3 stimulates Dnmt1 activity. Here, we show that monoubiquitinated histone H3 stimulates Dnmt1 activity toward DNA with multiple hemimethylated CpGs but not toward DNA with only a single hemimethylated CpG, suggesting an influence of ubiquitination on the processivity of Dnmt1. The Dnmt1 activity stimulated by monoubiquitinated histone H3 was additively enhanced by the Uhrf1 SRA domain, which also binds to RFTS. Thus, Dnmt1 activity is regulated by catalysis (ubiquitination)‐dependent and ‐independent functions of Uhrf1.